This proposal is for development of the patient oriented research career of Kyle B. Womack, MD, an assistant professor of Neurology and Psychiatry at UT Southwestern. Dr. Womack has received training in general neurology, molecular biology and, most recently, in behavioral and cognitive neurology. With the support from this award, he will be able to develop necessary skills in biostatistics and advanced neuroimaging procedures such as magnetic resonance diffusion tensor imaging (DTI). With the additional research experience, skills and momentum from this award, he will expand his career in patient oriented research, utilizing neuroimaging techniques and focusing on frontotemporal lobar degeneration (FTLD) as well as other neurodegenerative dementias. FTLD is usually conceptualized as a group of degenerative diseases resulting in neuronal loss and atrophy of specific cortical regions, but recent work has demonstrated white matter lesions are also present in addition to cortical atrophy. The purpose of this study is to explore the role and nature of white matter/axonal damage by identifying biomarkers for this type of pathology in FTLD. Dr. Womack will evaluate the utility of DTI, as a biomarker for FTLD in a cross sectional study of a cohort of well characterized FTLD patients and normal controls, identifying radiological characteristics that can distinguish these two groups. There will also be a longitudinal study with a follow up DTI scan after 3 years to ascertain the utility of DTI measures to follow disease progression. Post mortem evaluations will be sought on those who expire over the course of the study to both confirm the clinical diagnoses and to correlate quantitative measures of axon density with the DTI results from the same region. If DTI turns out to be a reliable and sensitive marker for FTLD it could improve the diagnostic accuracy for patients with this disorder. It is a relatively short MRI sequence that can be added onto the standard sequences in a clinical MRI, and requires no intravenous injections or exposure to radiation. Furthermore, a biomarker of disease progression may improve the power of relatively small, brief therapeutic trials. [unreadable] [unreadable] [unreadable]